As reminders…

Alpha–Variant first identified in the UK

Beta–Variant first identified in South Africa

Gamma–Variant first identified in Brazil

Delta–Variant first identified in India

Omicron–Variant first identified in South Africa

Updating the chart above:

Ancestral: B.1.1.529 Omicron (and cousins)

Transmissibility: All the +

Immune Evasiveness: All the +

Vaccine Effectiveness: Check (for hospitalization)

Also as a reminder:

Monkeypox

–Abbott, a major diagnostics manufacturer, announced that they would be making a rapid PCR assay for monkeypox. Other than that and some “what you should know about” headlines confirming that most of the monkeypox cases in question were sexually transmitted, monkeypox has fortunately, and deservedly, dwindled in the news in the past week. Even so, you are still getting hype articles about the ~500 total cases identified thus far, and “concern” that spread may increase, particularly in Europe during upcoming music festivals. Because somehow, they are NOT ahead of transmission chains yet. The news is still trying to make monkeypox pandemic a thing though. On the plus side, although preliminary, Google trends is showing a catastrophic collapse in monkeypox searches. And they remain a fraction of searches for COVID, even at this late date in the COVID pandemic.

Hopefully, they get in front of cases enough and public awareness through what was already out in the media is enough for the relatively small amount of cases for spread to level off in the low hundreds to thousands total.

Coronavirus

–Cases are dropping in most places in the world, believe it or not. Yes, they are even leveling off overall in the United States, if not starting a slight decline this past week. I think that may be a little underestimated (more on that in a second) because of mild symptoms and at home testing, but some of the early indicators like searches for COVID symptoms/treatments/tests etc. are coming down too. Fall bellweathers in the southern hemisphere like South Africa and New Zealand have seen level to dropping cases as well. China lockdowns have vanished from the news this past week, so they are presumably loosening up more and the omicron wave has crested there as well.

–All of that said, anecdotally, I have had at least as many friends and family within the last month either contact me about recently contracting COVID or tell me they had it recently within that time span as when omicron the original was running rampant around New Year’s. To a one, it has been described as an odd sinus infection, and/or a nasty hangover that caused them to pull out a rapid test which popped positive. No hospitalizations among those who reached out, but demographically, that is to be expected. The great majority could link their case to recent travel and large gatherings there, or conferences/large and well attended business meetings with participants traveling in from all over. In short, if a lot of people are traveling from everywhere to be together, there was a high probability of encountering one of the circulating omicron cousins.

Thus, I think the current prevalence of the omicron cousins is being grossly underestimated by the official stats, since these at home tests are undoubtedly very frequent and are not reported to the state health departments when positive.

Further, if that is true, than the hospitalization per infection (positive test rate) for these omicron variants is -very small-. Hospitalizations are only ticking up because there is still some risk, especially in those with underlying risk factors, coupled with the sheer force of numbers of everyone and their brother catching COVID again in the last month or so.

I am quite convinced by the available data and anecdote that the omicron cousins are highly contagious and capable of breakthrough of both prior infection and vaccination. Similar to omicron, they tend to be more mild. But again, hospitalization is still a risk, particularly for those in high risk categories. On a personal note, I am heading to an oncology conference soon which I expect will be well attended, with people coming from around the world. I will be wearing a mask a lot more–not because I am particularly concerned about my risk for severe COVID, but because I doubt even persistent high antibodies from vaccination are enough to guarantee protection from these variants and I really don’t have time for 3-7 days worth of hangover. A mask will reduce my individual risk by some x percent, so might as well pick up those points in what will be a high(er) risk environment for exposure.

Outside of that conference in the day to day though, I have not been masking for months.

Just remember, if you do pop positive for COVID, there are still many early treatment options available, ranging from the Merck and Pfizer pills (taken for 5 days) to the monoclonal antibodies (which are one and done, but require a needle and a little time at an infusion center). If you pop positive and are concerned, and certainly if you pop positive and have high risk factors for severe COVID, contact your physician about these early treatment options. Now that I am able to discuss a little more freely, I think the evidence is that they are all largely interchangeable in terms of reducing risk of hospitalization from COVID. To be more direct than usual, I would not take the Merck pill until I was 65 or older or until there is longer term follow up data available (like a decade’s worth). That is mostly theoretical concern about its method of action (deliberately causes mutation), and just one man’s opinion though. If long term follow up shows no increase in neoplasia among those who took it (and it’s only a 5 day course–I will concede the chance of neoplasia in that short an exposure window is very small), my opinion will probably change.

–Speaking of feelingsball and COVID, Pfizer got FDA approval for a booster shot of its vaccine in the 5-11 age range cohort. The CDC has yet to weigh in a recommendation, but that decision can be expected fairly soon.

It’s probably worth mentioning our coverage of JAMA article in our last update, which looked at vaccine effectiveness in the 5-12 age range. The ability of the vaccine to stop omicron symptoms in kids 5-11 after one month, which one might argue as evidence that a booster is a good idea. On the other hand, there was no reporting about a drop in vaccine effectiveness against hospitalization from COVID, almost certainly because kids in this age range, absent serious underlying immunodeficiency or other major chronic illness as a risk factor, are almost never hospitalized with severe COVID. They didn’t have enough hospitalizations in this age range to run those stats.

And again, for the eleventy-billionth time, prevention of hospitalization and death is the most important metric when evaluating vaccines or treatments for COVID. That’s the pandemic threat of the virus.

So it’s a little tough to say how truly necessary the booster is in this age range, absent those kids with serious underlying risk factors. Much will again come down to your own risk:benefit calculations for your kids, and I will not judge or fault you either way.

For what it’s worth, only 30% of kids age 5-11 in the US have received the initial two dose vaccine. I would expect booster shot uptake in this cohort, outside of those with serious underlying conditions (who will hopefully be 100% uptake of boosters because they need ’em), to have even lower uptake.

–In other vaccine news, both Pfizer and Moderna turned in data for vaccination of the under 5 cohort. The FDA will be convening its public advisory boards in June, tentatively June 15th. Following the advisory board, the FDA will make go/no-go decisions, and if the FDA says go, it’s over to the CDC for recommendations or not. Until the data is made public though, not much to say at this point.

–Going back to mask use both public and private, the New York Times had quite the write up on Tuesday morning conceding that mask mandates have done little to stop the spread of COVID from a public epidemiology stand point, but when used (and used properly) do reduce your individual chances of catching COVID by at least some few percentage points.

If that sounds suspiciously familiar, we were making that exact argument as recently as a year ago. You can find those sections here and here. And that was just me being lazy and grabbing two recent-ish mentions of this argument.

Again, we’re glad that the NYT is apparently catching up to our back pages. They have a far greater reach than us. However, Maybe Not So Hypothetical NYT Reporter Reader, feel free to just go ahead and drop a citation of the website in there. We don’t do SEO here, so anything helps the traffic.

–Just wait until the NYT catches on to the fact that what is true for masks (effective at stopping spread at the personal level, but not the public) is arguably true for the vaccination campaign as well, since it does not stop symptoms, but only reduces deaths/hospitalizations. You can refresh yourself on that here.

–In other coronavirus science news, the circulating cousins of omicron, particularly BA.2.12.1 in the US and BA.4 and BA.5 in South Africa, contain mutations that were also present in the delta variant. While the caused some mild hand wringing in some news articles this week, there is nothing at all to suggest rates of hospitalization and death similar to the delta wave. In fact, there are pre-print studies suggesting patients who recovered from delta may have improved natural immunity to these current omicron cousins, with less chance of breakthrough.

Frustratingly, these papers continue to talk mostly about currently circulating antibodies and B-cell mediated immunity as the measure of current “immunity.” That breakthrough cases are not resulting in hospitalization is in part due to reduced virulence of these strains but also undoubtedly due to memory B- and T-cell responses.

–In the final science-y bit, there is now active discussion on renewing the ban on gain of function research versus increasing oversight of grants supporting this kind of research–and extending restrictions over other organizations that research dangerous pathogens, and thus might conduct gain of function research. These range from pharmaceutical companies to philanthropic organizations (the Wellcome Trust, while UK based, does a lot of work on antibiotic resistance, for example) to the US Departments of Agriculture and Defense. You can find coverage of the debate in this Nature news article from early last month.

As we have discussed before, there is theoretical advantage to creating more contagious or more virulent strains of bacteria/viruses/fungi to understand how they might become worse, and thus have an early lead in treating them if they ever actually do become worse in the wild. This is what proponents of this kind of research cite for support. However, the risks of this research are considerable, and no matter the level of precaution taken, it is a question of when not if a lab modified, gain of function pathogen escapes the lab. And no, Hypothetical Reader, don’t @ me with the “it already happened in Wuhan, I thought?” Again, although there is a chance that happened, definitive proof is a long time, if ever, coming.

So as we wait for the governmental gears to grind on the decision to re-impose bans on support of gain of function research, and/or extend them beyond just the government agencies, it’s worth reviewing why gain of function research will inevitably end with a leaked lab grown pathogen at some point. Dinosaurs and Jeff Goldblum on screen quotes at the link.

But before we leave this section, we hope you caught the part near the end of that Nature news article which mentioned that more labs around the world are capable of gain of function research. That’s not necessarily because more labs are getting into it. That’s mostly because the ability to do gain of function modification is becoming easier and easier. Swapping a gene of choice into a plasmid, creating copies of it, and then injecting it into other bacteria is a literally a paint by numbers kit and could be done by someone competent with a bachelor’s degree. All you need is the gene you want to test as gain of function and the bacteria you ultimately want to put it into (the bacteria in the linked kit is just to create lots of copies of the plasmid you will use to put the gene into your true target bacteria). Or you can just skip that part, order the gene you want to test for gain of function online and get delivered in one of many convenient options to insert into your bacteria/virus/fungus of choice. Gene editing tools work reasonably predictably well in bacteria too.

My point is that even if the US bans support of gain of function testing, that does not mean it will disappear from the world. Or that the road to hell will not be paved by the good intentions of those believing the benefits exceed the risks and going around the ban to some of these labs in other parts of the world where oversight and questions about what the lab is actually doing are less…. stringent. Think about that kerfluffle during COVID where a group of Ohio State affiliated researchers got an experiment done where sandflies were biting immobilized dogs in an ethically questionable study design by having the actual work done in Tunisia. Or how Dr. Fauci’s section of the NIH still finds itself with some tough questions about improper oversight of a contractor who was doing gain of function research with the Wuhan Virology lab. The techniques and knowledge are too easy and too widely available for gain of function testing to NOT be happening somewhere in the world, at some point–even if it has to be done at the margins.

One argument not made yet, but likely to be, is that if this kind of research is so inevitable, why not conduct in the open in the labs with the best controls and oversight? After all, if it is condemned, and driven to the dark labs because there is less oversight there, does that not invite a greater risk of accidental release of something horrible? That’s a reasonable argument to make. But again, the problem is the inevitability of the math, even for the best regulated and controlled and careful lab we can imagine.

If the risk of a bad outcome is true ruin, there are no odds at which it is truly safe to play.

Sadly, that has not stopped humanity before, and likely won’t this time either where gain of function research to create more dangerous pathogens is concerned.

Socioeconomic

–Sri Lanka has been unable to import essential food, fuel and medicine according to reports this past week. This will only be the first time you read about problems like this in the world as this year grinds on.

–Anecdotally on energy production issues, I have heard from people who would know that you are in the sweet spot for shale oil and natural gas production in terms of proven reserves ready to be tapped and the current price they would get. The rigs are ready, they have employees ready to go.

They can’t though, at least not at the scale you would expect.

The problem is the missing widget, and it appears to be slightly different for everyone. For example, a particular form of sand that is needed for some of the shale oil/nat gas extraction simply cannot be sourced or delivered right now. This is the exact cascading disruption that we mentioned would be the supply chain risk at the start of the outbreak as individual countries or cities were shutdown for COVID or had unusually large and sustained sick call offs as the pandemic came to town. Some of them, tough to know who and where or when, but some of them would be THE major producer of a given widget. The absence of that widget would disrupt the supply of some other good elsewhere, the sudden absence or price spike resulting would affect ability to make yet another widget further down the line. And on and on.

And energy is a very important widget as we have stated before.

To say nothing of the now extremely likely cascade of missing widgets as various countries continue to get protectionist on energy and food supplies, restricting exports to ensure that they have enough of both to last this bad moon rising. Those countries who cannot source or keep enough food and energy in house are highly likely to go the way of Sri Lanka–and you can bet at least some of them will turn out to be significant widget makers. Where, when and who, I cannot predict. But the dramatic increases in the cost of food, and likely inelastic supply of both food AND energy throughout this year will result in geopolitical upheaval. Which will beget more supply chain issues in a very global, yet surprisingly fragile, system.

Meanwhile, as Twitter put it best recently, we seem doomed to repeat every bad policy decision of the 1970s in response to energy (among other vital commodities) supply crisis.

–A couple economic think pieces: 

On how you get inflation in a scenario where supply is constrained, and then has trouble responding to increased demand:

https://thelastbearstanding.substack.com/p/to-reap-and-sow?sd=nfs&s=r

On how to make diesel, why the US is running short of this mission critical fuel for agriculture and basic supplies, and why you might not be surprised if the US bans diesel export before the end of the year:  

https://doomberg.substack.com/p/grim-diesel?s=w

–Making some headlines in the past couple weeks, the US government has put forward a proposal that would actually increase WHO powers in the case of a pandemic, which you can read here. It’s not as dense as you might expect.

Most of it, to be honest, seems aimed at China’s lackluster early response and obfuscation, and seeks to compel greater host nation co-operation from a nation that may be experiencing a potentially contagious disease outbreak. It will also allow the WHO to share more information earlier, without the permission of the host country if necessary, as well as use data obtained from other nations that may be relevant to the outbreak in making its determinations of contagious/pandemic risk and recommendations for responses (which might include recommended travel restrictions etc.).

On the one hand, yes, this is one possible response to China sitting on vital data and obfuscating that SARS-CoV-2 had gotten loose on their watch and was spreading across borders, leading to a global pandemic. On the other hand, the WHO did not exactly cover itself in glory, and took a LONG time to feebly condemn China’s early responses. Eventually. After praising China in the early days of the outbreak.

We mentioned at the time that was likely due in no small part to how the WHO is financed, which is mostly through assessed contributions best read as “charges to the world’s nation based on their GDP and adjusted for WHO membership”. You can read the most recent available report on the WHO website for collection of those assessed contributions from just prior to the COVID outbreak here, but I will skip to the important parts for you. The United States contributes more than the next two highest assessed contributors (Japan and China, in that order) combined. Human organizations being human organizations, they don’t tend to bite the hand that feeds them. Hence, as we said at the time, the relatively …generous… public treatment of China’s early COVID response was not surprising given the amount of money China puts into the WHO.

Coupled with the existing language for the WHO’s pandemic responses, which require a LOT of permission and checking with the affected host country first.

So while the proposal does some good in removing the need for those permissions in the interest of global public health, let’s take Popper’s view and assume the worst people will come to head both the WHO and the government paying most of the WHO’s bills. Are there sufficient checks to the damage they could do? In this thought experiment, we don’t even need to assume the worst people are running those shows. In fact, we will appeal to the angels of the better natures and convince them to do their nefarious worst for a higher good.

So let’s assume that some douche in the heart of the former Soviet Union hauls off and invades a smaller neighbor on questionable pre-text, gets crushed in the early days, and settles into massed artillery fires into cities, civilians be damned, to advance. We’ll call him Vladimir P. — or better yet, V. Putin, just to keep it a little anonymized. Let’s assume the rest of the world is scandalized by this, and seeks to apply as much pressure as possible to stop V. Putin. Under these proposed amendments, how might we get the WHO involved? Well, we could have the big hearted leader of a country paying a very healthy chunk of the WHO’s bills call the Director General. The Director General is going to take that call. Our leader will then appeal to the better nature of our Director General, persuading her to take action as well to do anything and everything in their power to stop V. Putin. Perhaps they could declare an outbreak of a newly discovered disease, douchebagitis, which happens to be in the former heart of the Soviet Union? Or just the risks of pandemic disease from the ongoing activity and humanitarian disaster from the fighting? If other countries provided data on say, the spread of typhus in the war zone, or convincing “evidence” of douchebagitis, perhaps our Director General could lay down some recommended travel and trade restrictions–in the interest of public health?

In the reading of these proposals, there is nothing stopping this. Now, how enforceable any of those travel and trade restrictions might be, I’m not sure. But at its worst, this would provide the opportunity for shenanigans, in the unlikely event that there was a persuasive country looking for an unusual club to wield against its enemy, and a compliant Director General of the WHO persuadable to swing it.

But it does not merit some of the more extreme, and <sigh> expected, “new world order-esque” treatments where the WHO can override host countries and impose quarantines and lockdowns and the like that this got in some quarters of the internet. The WHO simply does not have that kind of power. If you doubt that, imagine this passes and the WHO demands that Putin be quarantined in total isolation as a pandemic threat of douchebagitis as its only known patient. How does the WHO enforce that within Russia where Putin actually gets locked up–because the WHO said so?

If anything, I think China’s response to these proposals will be interesting, and probably worth some popcorn. After all, this is not very subtle criticism leveled directly at the CCP’s total COVID response since 2019 and its propaganda about how awesome it has been doing.

–Speaking of other dubious centralizing power ideas, reports out of the World Economic Forum meeting have stressed the high likelihood of central bank digital coins as a way for central banks to settle balances between themselves. This follows papers released by the Bank of International Settlements released early last year, bemoaning the friction and high cost of settling international trade under the existing system, diagrammed here:

To make a very long story short, the preferred solution of the authors is this:

…with one centrally administered central bank digital currency to rule them all. That has rung alarm bells in some quarters, because yes, that last diagram in particular looks like a one world currency which would be issued and controlled by an otherwise unnamed central authority. However, as even the authors acknowledge, that requires getting EVERYONE on the same page to launch that, and it’s difficult to see, for example, North Korea opting to participate. After all, in that one world currency model, who controls the central administration controls the world. It would be far easier to kick Russia completely out of the global economic system to twist their arm to stop a war with that adopted. But applying Popper’s maxim again of imagining the worst possible people getting control of that lever means that any country, or people, would be at risk of getting unpersoned and with uncertain checks on that power, if a V. Putin were to one day find himself in charge of the one world currency.

Thus, for all the angst about the New World Order, getting enough central bank participants into that system will be a long grind, if ever achieved. What is more likely is this model from the author’s paper:

…where instead of the current system of exchanging dollars to euros when you order something online from Europe through a system of banks that have to be open, have accounts with each other, and enough currency to exchange to complete that transaction, you have the dollar tied to the US central bank digital coin traded instantly 24/7 in an online clearing system for the euro central digital bank coin, and the merchant you bought from can exchange into euros at a known, fixed exchange rate.

That central bank digital coins are coming, at least for this purpose, seems a foregone conclusion, as the CEO of Mastercard was quoted as expecting to see them within 5 years this past week. That’s a little different from a fully digital currency, the risks of which we have covered before, as well as the reasons a digital currency won’t happen or might circumvented if it is. Instead, this seems to be just a way of calculating reserves in banks on a digital ledger. Does this make economic sanctions on wayward states easier (and thus also possible to abuse)? Yes, and any nation that cannot produce everything its economy needs domestically (and I cannot think of a single nation, the US included, which can) risks going the way of Sri Lanka at the moment if you piss enough of the world, or whomever controls central clearing, that they flip the switch to cut you off from clearing international trade. Also makes for a great future Bond movie plot, where the evil villain hacks the central clearing and freezes it, paralyzing global trade with the threat of Sri Lanka everywhere.

But this seems to be where we are headed.

–On the one hand, I get the impulse for greater centralization, especially on a global level. In the very long game, assuming humanity gets there, the sun will eventually die and in its death throes will expand to swallow the Earth. If humanity does intend to last to the end of the universe, Elon Musk is not wrong when he says that we must eventually colonize space. That will require the entire globe working as one, and even then, it’s not immediately obvious that the laws of physics and resource constraints will make that possible. The distances in space are just mind blowing. For example, Voyager 2 left the solar system 32 years ago and has traveled 12 billion miles, give or take. That’s 0.002 light years. The closest star to the Sun is 4.24 light years away.

So if you’re playing the long, long, long game, then yes, humanity will have to recognize the humanity in each other for the first time ever in history, seeing one another as brother and sister no matter the differences, and truly doing unto one’s neighbor as one would do to themselves just to marshal the resources necessary to get us off the planet. Moves to unite the globe ever more, and convince those acting like douchebags to act right a little easier, are understandable.

If we take the charitable view that this really is the intended goal of some of these proposals, and not merely ways to punish another nation state you are annoyed with easier, or make it easier for cross border transactions that large international businesses can extend more market share and make more money. It’s possible our current leaders and institutions are thinking 100,000 years ahead, right?

On the other hand though, look at the leaders our current system tends to select around the world. Look at the values their actions, both public and private (when known), reveal. Action, after all, is more honest than words and more revealing of true values. And so I also get the suspicion of any effort to increase centralized power, because the way we run things now, on maximum stupid, has tended to select for maximum stupid. And so much venality. Yet we continue to propose handing more powers to the people and institutions that fell into the bonfire of the credibilities. This seems to be madness, does it not?

Our selection criteria for our leaders, who and how they act, is what we need to fix first. After that, we can talk about the necessary institutional reforms. Easier to say that than achieve it though, and that is why I suspect we will be here, between a brighter, more free future and dystopian failure, for at least this decade.

–Your chances of catching coronavirus are equivalent to the chances V. Putin really does have a terminal case of douchebagitis.

<Paladin>